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dc.contributor.authorSkaare, Dagfinn
dc.contributor.authorAnthonisen, Inger Lill
dc.contributor.authorCaugant, Dominique A
dc.contributor.authorJenkins, Andrew
dc.contributor.authorSteinbakk, Martin
dc.contributor.authorStrand, Linda
dc.contributor.authorSundsfjord, Arnfinn
dc.contributor.authorTveten, Yngvar
dc.contributor.authorKristiansen, Bjørn-Erik
dc.date.accessioned2014-07-07T08:20:40Z
dc.date.available2014-07-07T08:20:40Z
dc.date.issued2014
dc.description.abstractBackground Beta-lactam resistance in Haemophilus influenzae due to ftsI mutations causing altered penicillin-binding protein 3 (PBP3) is increasing worldwide. Low-level resistant isolates with the N526K substitution (group II low-rPBP3) predominate in most geographical regions, while high-level resistant isolates with the additional S385T substitution (group III high-rPBP3) are common in Japan and South Korea. Knowledge about the molecular epidemiology of rPBP3 strains is limited. We combined multilocus sequence typing (MLST) and ftsI/PBP3 typing to study the emergence and spread of rPBP3 in nontypeable H. influenzae (NTHi) in Norway. Results The prevalence of rPBP3 in a population of 795 eye, ear and respiratory isolates (99% NTHi) from 2007 was 15%. The prevalence of clinical PBP3-mediated resistance to ampicillin was 9%, compared to 2.5% three years earlier. Group II low-rPBP3 predominated (96%), with significant proportions of isolates non-susceptible to cefotaxime (6%) and meropenem (20%). Group III high-rPBP3 was identified for the first time in Northern Europe. Four MLST sequence types (ST) with characteristic, highly diverging ftsI alleles accounted for 61% of the rPBP3 isolates. The most prevalent substitution pattern (PBP3 type A) was present in 41% of rPBP3 isolates, mainly carried by ST367 and ST14. Several unrelated STs possessed identical copies of the ftsI allele encoding PBP3 type A. Infection sites, age groups, hospitalization rates and rPBP3 frequencies differed between STs and phylogenetic groups. Conclusions This study is the first to link ftsI alleles to STs in H. influenzae. The results indicate that horizontal gene transfer contributes to the emergence of rPBP3 by phylogeny restricted transformation. Clonally related virulent rPBP3 strains are widely disseminated and high-level resistant isolates emerge in new geographical regions, threatening current empiric antibiotic treatment. The need of continuous monitoring of beta-lactam susceptibility and a global system for molecular surveillance of rPBP3 strains is underlined. Combining MLST and ftsI/PBP3 typing is a powerful tool for this purpose.en
dc.identifier.citationBMC Microbiology (2014), vol. 14:131en
dc.identifier.cristinIDFRIDAID 1133980
dc.identifier.doihttp://dx.doi.org/10.1186/1471-2180-14-131
dc.identifier.issn1471-2180
dc.identifier.urihttps://hdl.handle.net/10037/6473
dc.identifier.urnURN:NBN:no-uit_munin_6073
dc.language.isoengen
dc.publisherBioMed Centralen
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical microbiology: 715en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk mikrobiologi: 715en
dc.titleMultilocus sequence typing and ftsI sequencing: a powerful tool for surveillance of penicillin-binding protein 3-mediated beta-lactam resistance in nontypeable Haemophilus influenzaeen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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